Agenus' CEO Discusses Q4 2013 Results - Earnings Call Transcript

| About: Agenus (AGEN)

Agenus, Inc. (NASDAQ:AGEN)

Q4 2013 Earnings Conference Call

March 5, 2014 11:00 AM ET


Jonae R. Barnes – Vice President-Investor Relations and Corporate Communications

Garo H. Armen – Chairman and Chief Executive Officer

Robert B. Stein – Chief Scientific Officer


John S. Sonnier – William Blair & Co. LLC

Mike King – JMP Securities

Jason H. Kolbert – Maxim Group LLC

Graig Suvannavejh – MLV & Co. LLC

Ren Benjamin – H.C. Wainwright


Good day, ladies and gentlemen, and welcome to the Agenus fourth quarter and full year 2013 conference call. As a reminder, today's conference is being recorded. At this time, I would like to turn the conference over to Jonae Barnes, Vice President of Investor Relations and Corporate Communications. Please go ahead.

Jonae R. Barnes

Good morning everyone. Welcome to Agenus conference call to discuss the fourth quarter and full year 2013 financial results. With me today are Dr. Garo Armen, Chairman and Chief Executive Officer; Dr. Robert Stein, Chief Scientific Officer; and Christine Klaskin, Vice President of Finance. During this call, we will provide a corporate update. We will then open up the call to questions.

But before we continue, I would like to remind you that this conference call will contain forward-looking statements, including statements regarding the company's potential income stream, development and commercialization efforts, timelines, availability of data and potential efficacy and market potential with respect to products and product candidates of the company and its partners.

These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. Reference to these risks and uncertainties is made in today's press release and they are disclosed in more detail in our most recent filings with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this call and Agenus undertakes no obligation to update or revise these statements. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. When evaluating Agenus' business and securities, investors should give careful consideration to these risks and uncertainties. As a remainder, this call is being recorded for audio replay.

With that, I will now hand the call over to Dr. Garo Armen, CEO and Chairman.

Garo H. Armen

Thank you Jonae. Before I begin my updates, I would like to take a moment to welcome Dr. Robert Stein to our quarterly teleconference. Dr. Stein was recently appointed for the newly created position of Chief Scientific Officer at Agenus. He brings over 30 years of experience and accomplishment to the Agenus leadership team. He is an innovative and experienced executive with deep broad knowledge of biology, medicine and pharmaceutical science.

This is an exiting time for the company and Dr. Stein is playing a key strategic role as we expand our immuno-oncology efforts into the checkpoint field. We’re delighted to have him on board and you will hear his remarks shortly on this call.

We began the year with the acquisition of 4-Antibody. This acquisition brings an exiting new platform of fully human checkpoint antibodies. This platform has already resulted in six preclinical programs in the most important area of immunotherapy, immune checkpoints. Immune checkpoints are processes that involve various genes that can inhibit or stimulate the immune system and therefore play a key role in how the immune system can control or defeat cancer.

We were able to consummate this transaction because 4-Antibody and their shareholders recognized our ongoing commitment to immuno-oncology and how our development capabilities would complement their research expertise. Both companies also share the same goal of creating truly transformational medicines to fight cancer using our combined immuno-oncology tools and expertise.

With the acquisition, we now have three compelling platforms; checkpoint modulators, anti-cancer vaccines; and adjuvants, all working on the same principle, harnessing the power of the immune system to restore the patient to health.

I am also delighted to report to you that in our efforts to fund our expanded portfolio, we raised $56 million during the first quarter of 2014. Our new shareholders include some of the highest quality institutional investors. With this, we are now in a financial position to expeditiously advance our immuno-oncology development programs. Our guidance for this year’s burn rate is between $35 million and $40 million.

As you will hear from Dr. Stein in a bit, we are already making tremendous progress with our new antibody platform in collaboration with scientists at Ludwig Cancer Research including Dr. Jedd Wolchok of the Ludwig Center at the Memorial Sloan Kettering. This morning, we announced that we were moving three checkpoint modulators into IND-enabling development and anticipate that we will advance additional checkpoint modulators in coming months.

I look forward to reporting our progress including securing at least one corporate collaboration during this year.

In addition to the benefit realized from the 4-Antibody acquisition, we are getting closer to realizing the potential financial benefits or another acquisition we made some years ago. With this acquisition came our adjuvant QS-21 Stimulon. Vaccines containing QS-21 Stimulon are getting closer to commercialization through our partnership with GSK.

This year, GSK expects to file for regulatory approval the first product containing QS-21 Stimulon, a prophylactic vaccine against malaria, the first malaria vaccine to show efficacy and qualify for regulatory filing. The malaria vaccine containing QS-21 has the potential to save the lives of hundreds of thousands of children in Africa each year. This vaccine candidate is an example of what QS-21 Stimulon can contribute and helps to explain why GSK has made it the backbone for a significant number of its vaccines in their development portfolio, including several late stage programs expected to have data readouts this year and next year.

During the first half of this year, we anticipate that GSK will report the Phase III results of their 2270 patient MAGE-A3 vaccine trial intended to prevent the recurrence of lung cancer after surgery. This therapeutic anti-cancer vaccine contains QS-21 Stimulon and has the potential to be a major step -- to represent a major step forward in the battle against cancer.

With these advances, QS-21 Stimulon is moving closer to generating royalty revenues for our company. Our potential royalties could be a significant source of non-dilutive funds for advancing our checkpoint modulators and other programs. We are entitled to receive milestone payments as GSK’s QS-21 Stimulon containing programs advance as well as royalties on its sales for at least 10 years after the commercial launch of the first prophylactic and the first therapeutic product.

Overall, QS-21 Stimulon containing programs with the exception of HerpV are funded entirely by our partners. These 20-partnered clinical stage programs benefit from their financial, development, and sales and marketing resources.

QS-21 Stimulon is a unique asset which represents a significant and an unusually diversified value driver for our company. We are also very pleased with the progress made without Prophage vaccines in glioblastoma, which you will hear more details from Dr. Stein.

Now, I would like to turn the call over to Dr. Robert Stein for a review of our scientific and clinical programs. Dr. Stein?

Robert B. Stein

Thank you Garo. This is a really exiting time for Agenus and more significantly for the millions of people battling cancer. Based on emerging unprecedented results from the clinic with checkpoint modulators, it is clear that the power of the immune system can be successfully harnessed to defeat cancer.

Agenus has been working in immuno-oncology for two decades, and Agenus’ recent entry into the checkpoint field through the acquisition of 4-Antibody positions us at the cutting edge of cancer treatment. CPMs or checkpoint modulators used alone and in combination are revolutionizing cancer treatment.

We know that the immune system is necessary to protect us against infection. We also know that too much immune activity can be debilitating or even fatal. In order to properly balance immune activity, the body has evolved a series of control systems, called immune checkpoints that regulate immune responses. While checkpoints normally play important roles in maintaining health, we are learning that cancerous tissues can highjack these processes to protect themselves from immune detection and immune destruction.

Monoclonal antibodies against checkpoints which are called checkpoint modulators are CPMs for short could be administered to patients to control the activity of specific checkpoint processes. By doing this, CPMs can restore the ability of the immune system to seek and destroy cancer. This is the basis for the great clinical success seen with CPMs like Yervoy which blocks the checkpoint protein CTLA-4, and Merck’s MK-3475 an antibody which blocks the checkpoint PD-1.

Scientific knowledge about checkpoints is burgeoning and we now know that there are many checkpoints in addition to the CTLA-4 and PD-1. CPMs directed against these additional checkpoints will play major roles in treating patients with a broad range of cancers. Furthermore, CPMs have the potential for use in other conditions, including chronic infections, autoimmunity, and transplant.

Unlike the response you’ve seen with chemotherapy radiation, the responses to CPMs appear to be more long-lasting, raising the possibility of converting cancer into a chronic or controllable and possibly curable condition. Some newer CPMs are agonist antibodies targeting checkpoint proteins, such as the receptors on T-lymphocytes called GITR and OX40. These agonist CPMs have the ability to stimulate antitumor immune responses.

The six checkpoint programs we now have through the acquisition of 4-Antibody target the six checkpoints of greatest interest in the immuno-oncology field today. We recently selected three monoclonal antibodies emerging from these programs to advance into IND-enabling studies in development including two GITR agonists and a CTLA-4 antagonist.

These molecules result from three years of intensive collaborative efforts among the scientists at 4-Antibody and the Ludwig Cancer Research Institute and Dr. Jedd Wolchok lab. Dr. Wolchok was pivotal in the development of Yervoy which is saving the lives of many patients with advanced cancer.

GITR is one of our checkpoint targets expressed at T-lymphocytes. It plays an important role in amplifying specific cellular immune responses including those against tumors. Many companies are seeking antibodies which activate GITR, but finding them has proven very difficult. We are very encouraged that the 4-Antibody platform is able to generate two high quality agonist antibodies suitable for development for this very challenging target.

And these antibodies have all the properties that we were looking for, and they are potent and selective. They turn on the receptor when they are buying to it and they have suitable pharmaceutical properties to make them less likely to fail during the next steps of development. They are easily both expressed at high levels, they are stable, they pull up properly and they have appropriate levels of glycosylation.

Checkpoint modulators like CTLA-4 and PD-1 antagonists used alone or in combination can make cancer more vulnerable to immune attack. It is also rational to combine CPM, such as CTLA-4 and PD-1 antagonists with anticancer vaccine such as Agenus Prophage vaccine, which are designed to enhance anticancer immune responses.

We are currently studying the combination of our vaccine Prophage with the CPM Yervoy in an ongoing Phase 2 trial in patients with metastatic melanoma. This trial is being conducted at the University of Texas. We believe well designed translational studies like this can improve the odds of success for our own CPMs and accelerate their clinical development.

We believe that with the acquisition of 4-Antibody, we have a top notch platform for generating fully human monoclonal antibodies with the pharmacological properties that can lead to effective products. In collaboration with our translational medicine partners at Ludwig Cancer Research, we plan to advance our emerging portfolio of CPMs as single agents and in optimized combinations, possibly including combinations of our anticancer vaccine and other agents for which there is a strong rational for synergistic effects of the CPMs.

In addition to our recently acquired monoclonal antibody platform and the CPM that is associated with it, Agenus has two other significant platforms for harnessing the immune system for therapeutic benefit. There are adjuvant platform build upon QS-21 Stimulon and our heat shock protein based vaccine platform. Both of these platforms have shown meaningful progress during 2013.

Several important QS-21 Stimulon adjuvant containing vaccine programs reported data during 2013 and our Prophage Phase 2 study in glioblastoma multiforme or GBM are particularly aggressive from the brain cancer continued to show encouraging clinical results. Regarding adjuvant QS-21 Stimulon our partner GlaxoSmithKline reported pivotal Phase 3 data on their malaria vaccine RTS,S.

GSK has indicated that we will file for registration this year. The results of this trial which involve testing approximately 16,000 infants and children in Africa demonstrate the safety and efficacy of this vaccine which contains QS-21 Stimulon as it’s adjuvant.

In Africa, malaria still claims over 600,000 infant and children lives each year and this vaccine could save potentially upto half that number. I’d say, very major advance for human health.

In other Phase 3 trials of vaccines containing QS-21 Stimulon GSK conducted a study in 1375 patients with malignant melanoma to determine if the vaccine directed against a tumor antigen called MAGE-A3, could prevent recurrences after a surgical removal of the primary tumor. While we believe that this vaccine has the potential to provide benefit to some patients, it did not reach statistical significance where all patients in the study were evaluated.

However in this study, GSK premeasured the levels of expression of a number of immune response related messenger RNAs in the tumors prior to vaccination. This may provide a way to determine which patients are more likely to benefit from the vaccination against MAGE-A3. This predictive test based on the defined gene signature suggest that roughly half the patients in the melanoma study were likely responders.

GlaxoSmithKline is now analyzing the results of this Phase 3 melanoma trial to determine whether or not the vaccine benefit is statistically significant in the subset of patients who are positive for the gene signature. The data are expected to be reported in 2015 and if the results are positive the FDA has agreed that this could serve as the basis for regulatory approval of the MAGE-A3 vaccine in melanoma.

Phase 3 trial is also vaccination against the tumor antigen MAGE-A3 in 2270 patients with previously surgically removed lung cancer are also expected during the first half of 2014.

In addition, another GSK vaccine containing QS-21 Stimulon is their shingles and we expect this to advance in 2014. In 2013 in the fall, GSK initiated a new Phase 3 study to evaluate the immunogenicity and safety of this shingles vaccine candidate when combined with their seasonal influenza vaccine and it’s over 50 years old. In total there were nine Phase 3 studies ongoing with this vaccine involving over 30,000 subjects. Results from these studies are expected to begin emerging in 2015.

Next, we reported preliminary results from our HerpV Phase 2 trial evaluating a heat shock protein based vaccine intended to treat genital herpes. The final data which include the results of a booster dose are expected to be reported during the first half of this year. In the preliminary results, we did see an effect of HerpV on viral reproduction.

HerpV contains QS-21 Stimulon and 32 herpes simplex virus related immunogenic peptides. Possible future efforts to develop HerpV will be based on our completed analysis of the study to date which we expect to have by the middle of the year.

Finally, I am very encouraged by the progress we are making with our autologous anticancer vaccine, Prophage in the treatment of patients with glioblastoma multiforme.

In patients with recurrent glioblastoma multiforme, we have seen that over 90% of the patients treated with Prophage were alive at least six months after the reremoval of the tumor and 30% lived for a year or longer. The median of overall survival is approximately 11 months. This compares to the expected median survivals in this group of patients of just 3 to 9 months.

These data were published in the journal of neuro-oncology in December and then an accompanying independent editorial Dr. John Sampson, who is a Professor of Neurosurgery and Immunology and Pathology at Duke University Medical Center called the results impressive and said they represent a potentially very promising therapy for patients with recurrent glioblastoma who are in desperate need of new treatments.

In addition, we also reported progress in the Phase 2 trial of Prophage in patients with newly diagnosed glioblastoma multiforme. Patients were treated with the standard of care, which involves surgical recession of the tumor, administration of the operating agent temozolomide and radiation. And additionally they were treated with Prophage vaccine made from their resected tumor.

The data although from a single ARM open label study show a median progression free survival of almost 18 months which compares to an expected survival of approximately seven months with standard of care alone. The median overall survival which was the primary endpoint of the trial was nearly two years when Prophage was added to the standard of care and this compares to approximately 15 months median overall survival expected from the standard of care alone.

Based on these findings in newly glioblastoma multiforme, we held an end of Phase 2 meeting with the FDA in February to discuss possible Phase 3 trial designs that could potentially lead to marketing approval of Prophage as a treatment for patients with surgically resectable newly diagnosed glioblastoma multiforme. We characterized it as a productive meeting where the agency generally agreed with our design of a single Phase 3 trial. If the data from this trial are positive, this could support a regulatory filing.

Also last year patients with recurrent GBM began enrolling in the ALLIANCE trial at 222 patient NCI sponsored randomized study of Prophage vaccine Avastin or the combination of the two. This is the largest brain tumor trial ever funded by the National Cancer Institute. We believe this trial is a major step forward in efforts to develop innovative new therapies for people battling brain cancer.

I will now turn the call back over to Garo.

Garo H. Armen

Thank you Bob. In closing, Agenus was founded for the purpose of revolutionizing the way patients with cancer and infectious disease are treated by harnessing the power of the bodies immune system. Not only have we remained steadfast in this pursuit, and to our commitment to immunotherapy, but we have continued to expand our arsenal called immunotherapy approaches.

To our own efforts to get there with those of our partners we will continue to advance our checkpoint modulators, heat shock proteins and QS-21 Stimulon adjuvant programs. We believe that we are well positioned to develop a new generation of novel and competitive immunotherapy based treatments with the potential to drastically improve a patients disease outcome and their quality of life.

Thank you for your continued support and interest in our company. We hope that you have found this update helpful and that will conclude my remarks and I think we’re open to take any questions.

Question-and-Answer Session


Thank you. (Operator Instructions) The first question is from John Sonnier of William Blair. Please go ahead.

John S. Sonnier – William Blair & Co. LLC

Hey, thanks for taking the question. Garo, obviously a very exiting time for you guys. Congrats on all the progress. I have a couple of questions, the first is really kind of a bigger picture question. If you look forward a year or two – when you’ve gone through your strategic planning process, what do you want this to look like? Do you become kind of an oncology-focused company where you try to hang on to these earlier stage assets to a point in time and partner them? Do you monetize HerpV and try to keep things all the way to market? What is the goal ultimately for Agenus with this acquisition and kind of how you think about moving forward?

Garo H. Armen

Well, John, if you look at the historical make up of our company, there are really -- the key drivers had been immunology and oncology. And I think it’s reasonable to assume that going forward those will remain the key drivers of our company. As we get closer to potential commercialization of our product, we will most likely want to be a company that would at least be in a position to be able to commercialize small specialty cancer products in the field of immuno-oncology. And if you look at our portfolio right now, it is comprised of a very broad portfolio of checkpoint modulators. And I think it’s reasonable to assume that some will be licensed out and others will be kept for the benefit of our own company, and we will take that through the development process.

In terms of other applications outside of the immuno-oncology field, such as, as you remark the herpes vaccine, we would like to take these to a point where they are partnerable because our core expertise doesn’t cover this area. And I think it would be reasonable to assume that a company like us, our size and scope would be unwise to invest the kind of effort to build an expertise in an area which has not been our sweet spot.

John S. Sonnier – William Blair & Co. LLC

That’s actually very helpful, and a question, I guess, Garo for you or Bob, if I look across this rapidly, rapidly evolving immuno-oncology space, there is some duplicative efforts with some of these checkpoint inhibitors across the industry. Can you talk a little bit about both what the IP landscape looks like and that would be particularly interesting with CTLA-4? And then with CTLA-4 specifically, where you plan to go that might be different than maybe an area that Bristol would go readily?

Garo H. Armen

Let me just address very briefly the business aspects of your question and then I’ll turn it to Bob to delve into the IP and other considerations. But, as you know John, checkpoint inhibitors and checkpoint modulators are broadly applicable and they are applicable not necessarily to one type of cancer, but a whole bunch of different types of cancers. One of our strategies will be to chase after smaller indications that perhaps are not in the radar screen of the large players in the field for which a sales or commercial opportunity maybe a lot more meaningful for us even if it’s a smaller opportunity than it would be for the larger company. So there are a lot of niche indications that we will be looking at and in fact we are looking at, which we will use to position our products for the purposes of our own portfolio, our own efforts to develop and commercialize, and obviously the larger indications we could do in collaboration with the larger companies. Bob, why don’t you address the more technical and the IP question.

Robert B. Stein

Thank you, Garo. Hi, John, into the questions, we are glad that we have a portfolio of checkpoint modulators because the future of this area isn’t going to be just pumping Yervoy plus a PD-1 inhibitor into every patient. You’re going to have to understand which processes are active in a particular patient and have the right combination of interventions. These are very powerful and very effective ways of intervening, but they also have side effects, and it’s not justifiable to produce those side effects in people for whom that checkpoint isn’t crucial.

So,we like the fact that we have a portfolio, combinations will be important. As you pointed out, it’s highly, highly competitive. We are in the same six targets that most of the larger companies are interested in. The good news is that we began to work on them three years ago because Jedd Wolchok and the Ludwig were involved in the selection of the targets and they were at the point where they could see the future very clearly.

On two of the targets, GITR agonists and OX40 agonists, we’re at or near the front of the pack. For two, we’re sort of in the middle of the pack with the others, TIM-3 and LAG-3, and for two we’re probably behind the pack with PD-1 and CTLA-4. But we do have strategies which will allow us to advance all these programs.

You heard a little bit from Garo about one of those, which would be to go after cancers of meaningful prevalence, but not the obvious lung cancer, colon cancer, breast cancer space. There are at least half a dozen fairly common tumors that may not be the first place that the larger pharma companies pursue.

Second, we have the option taking them into geographically novel settings, which are not the first places the other people will go and we have a very strong alliance with the Brazilian biotech company receptor, which has the mission of building an Agenus biotech capability in Brazil.

And third, we have the possibility of combining our programs with our autologous vaccine programs and that’s a place where we have fairly clear open landscape. The IP situation is quite complex and that’s pretty well they are scattered mine fields. We’ve done a very job and I might say we are really need the people for antibody in taking into very sophisticated account, the intellectual property landscape to both fine tune to operate and achieve composition of matter patents.

With regard to CTLA-4, the IP is a little bit complicated because Bristol as a patent, the patent of exposure of the antibody in the body. It’s a PK related patent. But we believe we have a way out of that with our version of CTLA-4, which we think is substantially more potent than Yervoy.

John S. Sonnier – William Blair & Co. LLC

All right, thanks a lot.


Thank you. And the next question is from Mike King of JMP Securities. Please go ahead.

Mike King – JMP Securities

Hi, good morning thanks for taking the question. And just sort of related question to John regarding the 4-Antibody technology. We are new to the name and was not a company that was familiar with most investors. I am just wondering how do investors gain insight into the quality of this technology, the quality of these antibody, their activity, their capabilities, what kind of things can we look at that would give us comfort that the antibodies that you’ll select will be competitive on a world stage?

Garo H. Armen

Let me address this broadly and then back to Stein perhaps will get into some details, but not detail enough to give you or to publically disclose our competitive position. So in terms of how do you get comfortable with it. Well there is certainly some publications by our scientists that are into public domain which we have circulated to people.

In addition to that I think the biggest comfort level is because of our association with Ludwig and Dr. Wolchok’s whereby these institutions are the leaders in the field and clearly as we have stated the collaboration between us and them has resulted in certainly the lead programs that we are pursuing.

Now one would ask if Ludwig and Dr. Wolchok’s lab as the leaders in the field have a choice of pickings why would they pick our portfolio and I think that’s a question that you need to put to them.

But beyond that, Dr. Stein, would you like to elaborate on the intricacies of what this technology is.

Robert B. Stein

Mike, it’s a good question. There are a lot of different ways to generate antibodies and I just happened to like the 4-Antibody platform very well. It’s analogous to phage display or something similar in yeast, but the main difference is that they utilize mammalian lymphocytes as the cell type in which to do the combination of heavy chains and like chains to find the antibodies that have the selectivity that you’re seeking. And this has some very useful aspects.

I would like to point out first off, this is extremely hard to get put together, it took them almost seven years and over $50 million expended. Company has been in existences for 10 years and they really took in the first 7 years of their life to get it to the point where it really works very well and now it does. When you select antibodies this way in mammalian cells in particular in these B-lymphocytes. They are much more likely to have appropriate properties for subsequent development.

You don’t find something that binds your antigen and then help to figure out how to turn it into an antibody. Second of all, because of the details of the platform these antibodies are very readily analogued to optimize their properties both their pharmacologic properties and their pharmaceutical properties.

And so it’s a very powerful platform, I actually wouldn’t trade it for any of the others that are out there. I am familiar with those.

And it was sort of a hidden gem, it is described in a very good publication they call it Retrocyte Display, and I’m sure that Jonae can provide that publication to those who are interested. And with regard to the pharmacologic characteristics and the details of the compounds you selected, we won’t be discussing that in great detail. It’s very hard to get to these endpoints. So we are not really prepared to go into a lot of detail with those until we’re further along.

But as Garo pointed out, the collaboration with the Ludwig Cancer Research and Jedd Wolchok’s lab is not a name only collaboration. There actually is a Joint Steering Committee, a lot of the experimental characterization of these development compounds has been done in Jedd’s lab. And he is very well positioned to know how they stack up in the world of potential competitors.

Mike King – JMP Securities

Got it and perhaps an important question, but let me ask anyway the – Bob you said it was a hidden gem, I mean if the technology, is as good as you guys are saying, why did you get so lucky, why was there not a major farmer, major biotech company that cooked them up?

Garo H. Armen

Mike, and your question is, you’re doubting what we are saying. Aside from that, I think it was a confluence of events that allowed us to be able to mundane this, one is the fact that as Bob said, this company had been around for a long-time. They fine tune their portfolio and their strategy back three years ago to get into this field.

Now being a private company, they had their challenges of funding their operations on a two string kind of a budget and I think perhaps it’s fair to say that the value of the company was being portrait at a much higher level than what our initial consideration was. And when I say initial consideration, I want to make it clear that for anybody, shareholders and the team their fortunate’s are very much aligned with how much value we create to.

Mike King – JMP Securities

Got it, right.

Garo H. Armen

So in essence we structured a deal with them which could end up making log multiples of what the initial consideration was and because of the creativity which we structured this deal, the other interested parties were not competitive and the other interested parties included major pharmaceutical companies.

Mike King – JMP Securities

Okay, yes, now that deal structure is certainly unique. Well, that’s fine, I think that’s adequate. Thanks very much.


Thank you. And the next question is from Jason Kolbert of Maxim, please go ahead.

Jason H. Kolbert – Maxim Group LLC

Thank you. It’s just as very interesting listening to this discussion. I think what Mike was alluding to was the fact that Novartis paid $500 million for stem and didn’t seem to get the same number of checkpoint inhibitors that you gotten. Clearly its’ exciting because of the scope and breadth of this pipeline.

I’d like to ask a little bit if Dr. Stein could talk just briefly about the study that you are doing with the University of Texas, only because that’s an area where we are seeing a combination with the checkpoint and help us understand kind of what you’ve learned from that study with Prophage and Yervoy and what you’re thinking in terms of what the next combination might be.

And of course this is really exciting when we look at melanoma, we look at glioblastoma. So just I understand it’s early days but help me understand kind of how you go about moving a combination forward?

Robert B. Stein

Thank you Jason. It’s a very good question. This is the exploratory translational medicine study. It’s obvious that Yervoy can help about third of patients who have metastatic melanoma. In the year 2000 and 2002, Agenus did a study in patients with metastatic melanoma with Prophage in which they saw a 45 patients had they had six who had stable disease, two, had really dramatic responses.

One of them, had widely dissembled melanoma and he was alive ten years later. And the curious thing is to try to understand why some patients respond and some patients don’t for either intervention, and it’s possible that some patients don’t have enough front-end recognition of the tumor is abnormal and some patients may have too much downstream tumor related defense to allow the immune recognition to result in tumor control.

So in this study we are looking at a combination of Prophage vaccine plus Yervoy in patients with metastatic melanoma. It’s 25 patients has being conducted by a very good investigator at the University of Texas. And we will be monitoring this study very heavily to extract all types of information with regard to the immune system and the interaction with the tumor. So that we can be smarter about designing subsequent studies. If we see an indication that Prophage and Yervoy synergizing these patients, then we have a natural place to take our own CTLA-4 agonist forward for registration studies. So we can pilot it out with Yervoy and for the situation where we’re heading toward registration, we can body and articulate for antagonist and we will now roughly at what level of CTLA blockade we need to dose in order to have a high chance of success.

So that’s a type of study where a prop study can help us to be more successful in the downstream activities. And other place where we see interesting suggestion that’s a combination of Prophage and a checkpoint modulator might be a useful combination is in the glioblastoma multiforme arena. In the study, we did in 42 patients with newly diagnosed glioblastoma multiforme.

We saw that if you stratify patients by their baseline level of the ligand for PD-1 not just PD-1 under a peripheral blood monocytes or in their tumor infiltrating macrophages which are derived in the peripheral blood monocytes. Those patients with PD-1, expression on their peripheral blood monocytes above the median do less well on the vaccine and those are added below the median.

So that suggest that they may be possible by combing Prophage and a PD-1 antagonist in the people with higher levels of PD-1 expression. We might be able to make them have results more comparable to the benefit seen in the patients added below the median. So there is some very natural places for us to think about combining the autologous vaccine approach and the checkpoint modulators. And this is an area where I think that there is a real opportunity to bring better results to patients.

Jason Kolbert – Maxim Group

That’s really helpful. Help me dove tail that with the work that Dr. Andy Parsa is doing it NCI and what the flexibility might be if that program advances, how can you catch up one of the checkpoint inhibitors to maybe look at a norm in that future program that might include a combination or maybe that’s not possible but help me understand?

Robert B. Stein

The future for that study I just mentioned the study briefly. Dr. Andy Parsa who is the chair of Neurosurgery at the Feinberg School of Northwestern is the principle investigator on that study. It’s being funded by the MCI to the equivalent of about $26 million worth of support for the clinical activities, so largest brain cancer study they’ve ever conducted.

And the design is 222 patients randomized into three arms, 12121. One arm is Avastin is in patients with recurrent clear of our multi-formulation metrics. And so one arm is Avastin, which is the standard of care. Second arm is Prophage, and if the patients progressed, then they will go in Avastin. Then the third arm is Prophage plus Avastin.

And that study can give us real insight into the effective adding Prophage to Avastin. And if we see an encouraging signal there, the future of that study is to take it from the Phase II study of this into Phase II, Phase III extension with the possibility of registration. And so we might choose to fund the Phase III part of that, but with substantially de-risk money because we’ve already know what the Phase II result look like.

Now, when people progress, there is the opportunity to try to understand whether they have kicked in some checkpoint process and that might guide us to where we might want to intervene beyond that plus we will baseline all these patients for the level of PDL1 expression on the peripheral blood monocytes. So they are maybe some opportunity to think about sub-stage. If you grow from that stage with investigate the combination of CPMs and widen both of these interventions.

Jason Kolbert – Maxim Group

Very exciting, thank you so much for the update. Congratulations on all the progress.

Robert B. Stein

Thank you Jason, I appreciate your interest.


Thank you. And the next question is from Graig Suvannavejh of MLV & Company. Please go ahead.

Graig Suvannavejh – MLV & Co. LLC

Thank you very much. Let me add my congratulations on the progress that you guys made as well. Several questions if I could, just keeping on the same of 4-Antibody, can you talk about potential combinations and beyond just obvious ones in terms of maybe combining some of your candidates with something like Yervoy or Prophage, are there any other ways that we should think about how you think about combinations from a rational perspective in terms of the types of combinations you want to be doing?

Robert B. Stein

Sure, Greg nice to talk you. So, we have the two agonists CPMs or GITR agonists and then we are not too far away from identifying OX40 agonists to take forward. Both of those are checkpoint systems are little different from PD-1 or CTLA-4. Those are systems that are T lymphocytes and they help amplifies specific immune responses against to find antagonists.

So, in the context of Prophage, we vaccinate people with a mixture of proteins derived from their own tumor and there is the opportunity that in conjunction with the vaccination, we might use something like you get our agonists or OX40 agonist to increase the specific immune response and send more armed sort of cytotoxic lymphocytes towards the tumor recognizing specific antagonists that’s one piece.

And the other thing is that some of those agonists have been reported to make this cytotoxic T lymphocytes less resistant to pressure by T regs regulatory T-cells which work in tumors and plus the attack of the tumor specific lymphocytes.

So, there are interesting opportunities to combine the vaccine with the agonists, it’s also possible that by combinations of chemotherapy or radiation therapy or natural tumor necrosis that we can enhance auto vaccinations. So, we can amplify the degree of recognition of the tumor as that normal by the application of these agonist antibodies.

And at the same time, there maybe downstream processes that the tumor has engaged to defend itself against attack. So, part of this is to figure out in each patient, which of these processes is extend and use the right combination of interventions to benefit that particular patient and that’s the way this field will trend, it’s going to take five years to get all figured out, 10 years from now the treatment of cancer will be profoundly different.

Graig Suvannavejh – MLV & Co. LLC

Very helpful. And just on the comment that you made earlier today, have those won the goals for 2014, is that you are hoping to sign a corporate collaboration. Maybe you could give us some thoughts on the ideal partnership in terms of what you’re looking for whether it’s the partner itself over the terms or just as you got this, maybe just a collection of assets, how would you think about partnerships?

Garo H. Armen

Well, I think that the nice aspect of having had a successful fundraising is we don’t have to sell these off for financial reasons. We can make intelligent decisions about what strategically will advance our chances of success. This is a very big, broad area and there is going to be intense competition. And it maybe that for some of these targets it make sense for us to find a partner who is going to help us, push it as aggressively as possible. But we have the capability of taking each of these forward through Phase 1/2 studies and we want to retain the opportunity to combine these in the appropriate ways to get clinical benefit. So we don’t want partnerships sequester these assets and remove our ability to work with them to get optimum clinical studies designed and carried out.

We do want somebody who has a deep and real commitment to the area and the attractive feature for us is that there are a number of parties who are clearly interested in what we have. Both those who have been actively engaged in the area maybe with some more interest on that ones where we’re more near the front of the pack and also from some of the large companies who now have woken up and realized that they may have missed the boat and have tried to jump in quickly like Novartis do with CoStim. So we’ll keep our options open. We have the goal of being able to get real medicines created out of this portfolio and being able to drive the effective use of combinations. Now it’s actually one of the drivers for Jedd Wolchok when he got involved in this whole interaction, was to be able to have the quiver fall off the appropriate arrows so that he can actually do if necessary in each patient.

Graig Suvannavejh – MLV & Co. LLC

Thank you. My last question is just on the 4-Antibody assets that you have, now that you’ve announced that you are moving three of them into kind of preclinical development. Could you perhaps give us a little sense of expected timelines on when we might be able to see data, whether it’s at a medical conference or when you might been in a position to maybe file INDs, just so we can get a sense of the process and how long it might take to get from where you are now to where we, as investors and analysts, might be able to see the quality of those assets?

Garo H. Armen

Sure, Greg. So the answer is for the three that we’ve identified, our intension is to move them through to INDs in the 15 to 18-month time frame. 15-month is aggressive. We hope that 18-month will be achievable, but we’ll push for 15-months. We expect to indentify additional development candidates for the other four targets over the next four to six months.

And so three years from now we hope to have 4 to 6 of the IND stage. And I think that’s realistic. We will decide what to disclose about these candidates from a standpoint of their activities and as it makes sense form the business standpoint to that, it’s such a competitive area, we are going to be pretty careful about that.

Graig Suvannavejh – MLV & Co. LLC

Thank you for all those answers, and again congratulations.

Garo H. Armen

Thank you, Greg.


The next question is from Ren Benjamin of H.C. Wainwright, please go ahead.

Ren Benjamin – H.C. Wainwright

Thanks guys for taking the questions and congratulations on the progress, lot of my questions have been answered, especially regarding antibodies and maybe I can just jump into Prophage you had mentioned that you broke with the FDA. Can you give us some sort of a sense, one of what the potential Phase III design could be and frankly given the acquisition, what timing you could tell us regarding as to when Phase III might start if at all?

Garo H. Armen

I think that the good news was that they were friendly to the idea of doing one pivotal Phase III. The guidelines are that these statistical significance for that has to be greater than p equals 0.05. The study design would have to be in my opinion, standard of care versus standard of care plus Prophage and the study size is still something that we are thinking about.

Our current belief is that we don’t intent to develop our money towards that at this point. We will entertain possible partnerships around that. We have the progression of the recurrent GBM study to monitor in the ALLIANCE trial and we can learn quite a bit about whether that is a wisest place for us to invest from the standpoint of return on investment compared to advancing our CPM portfolio, which is our main goal right now.

Ren Benjamin – H.C. Wainwright

Fair enough. And just regarding the ALLIANCE trial, is there any sort of an update or any sort of color you can provide us to how that trial is progressing and when we might be able to evaluate any of the data coming from that trial?

Garo H. Armen

So that trial was open for enrollment in June, it’s progressing reasonably well, the enrolment has picked up because not only was the ALLIANCE group supporting it, but now the radiation therapy oncology group has endorsed the trial and that’s brought the number of recruiting sites to over 550, which almost doubles the number that we are involved. So, we are hopeful that this will get – that the enrollment will be completed sometime before the middle of next year. And it requires about a two year observation period to get to the expected overall survival end point. So, we might see some data from that 2016.

Ren Benjamin – H.C. Wainwright

Okay. Regarding just upcoming milestone, obviously we have HerpV and we know some of the data milestones that are coming. But can you give us the sense of this presentation, data presentations maybe at ACR ASCO or anything else for 2014?

Garo H. Armen

So, we bring as you said there will be data by around the middle of the year for that the HerpV trial additional data. And as far as the other data related presentations, so for example anything on the GBM trials, we will have updates on those at the appropriate forms, but there is nothing specific that has been scheduled.

Ren Benjamin – H.C. Wainwright

Okay. And just one last question actually going back to 4-Antibody, you mentioned by that 15 months to 18 months and you will be hopefully filing an IND. Does that mean that in vitro and in vivo studies are currently being done or there are you’ve chosen the candidates and both sides the preclinical work are about to get started?

Garo H. Armen

That means that we’ve chosen specific development candidates about a month ago now for the three targets. The three candidates we mentioned, where in the process of doing the analytic work on those getting the stable cell lines built and the main hurdle that remains is after making enough material during the safety assessment studies in non-human primates.

And so it’s fairly the standard run up for antibodies to get them into clinical trials. And as I mentioned 15 month is a pretty aggressive timeline. We’ve already done the studies that we need to do to characterize the compounds with our pharmacologic activities. We will dome some PK, that’s modestly involved and we just need to get soon to the clinic now.

Ren Benjamin – H.C. Wainwright

Perfect. Thank you guys very much and congratulation.


Thank you. The next question is from Mike King of JMP Securities. Please go ahead.

Mike King – JMP Securities

Thanks for taking the follow-up. Maybe just further to the question you just answered for Ren, is there any possibility that you might be able to show some generic mouse study data prior to the filing of an IND of any of your candidates?

Garo H. Armen

Well, the mouse systems are only vaguely informative for human checkpoints. We have a lot of data with human lymphocytes and some materials derived from patients with cancer. There is a lot of work that has been done validating GITR as a target, using urine antibodies that are analogous to our. And that’s probably the best way to look at it. There are these reconstituted mouse systems that use human tumors and human lymphocytes can be put into them. But I don’t believe that that’s a necessary step on the pathway to getting these things into development. Really we have enough evidence that these are good points of intervention.

Mike King – JMP Securities

…and material.

Garo H. Armen

We are not alone and that there are many pharma companies that would have drug the [indiscernible] have active progress taking GITR agonists. This is one of one that’s most hardly being sort by partners who are coming to us with the interest in looking at our compounds.

Mike King – JMP Securities

Right, okay thanks.


Thank you.

Garo H. Armen

We wish that the mouse systems were more informative.

Jonae R. Barnes

Operator, I think we’ll actually end the call right here. A replay will be available approximately two hour after the call through midnight Eastern Time on May 05, 2014. The replay number is 416-915-1035 and the access code is 498676. The replay will also be available on the company's website approximately two hours after the call. Thank you very much for joining us today.

Garo H. Armen



Thank you ladies and gentlemen this concludes the conference call for today. We thank you for your participation. You may now disconnect your lines and have a great day.

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